Candidate: The candidate is an Assistant Professor of Medicine with a Ph.D. in epidemiology. He has exceptionally strong skills in the areas of study design, data analysis, and manuscript writing. He has had a longstanding interest in how depression affects cardiovascular health, and was lead author of a recent study of depression and incident heart failure that was published in the Archives of Internal Medicine. The candidate's immediate career goals are twofold: (1)Conduct a study which examines whether infectious pathogens mediate the link between depression and coronary artery disease (CAD), and (2)Enhance his research skills in ways that will foster his ability conduct future studies of depression and CAD. His long term career goal is to become an independent investigator conducting patient-oriented studies of depression and cardiovascular disease. Research Career Development Plan: The candidate intends to pursue a number of career development activities. The two most important activities will be as follows: (1)He will receive training in how to administer instruments designed to measure depression. These instruments will include the Structured Clinical Interview for DSM-IV (SCID) as well as the Hamilton Depression Scale (HAMD). After receiving sufficient training, the candidate will administer these instruments to participants in his study. (2)The candidate will acquire further knowledge in the area of personality and psychology and will develop skills in the area of statistical genetics. This will be accomplished by attending seminars, workshops, and classes. Research Project: The specific aim of the candidate's research project is to examine whether the association between depression and subclinical CAD is mediated by infectious pathogens. His project will be a substudy of an existing NHLBI-funded investigation ("The Twins Heart Study"). His project will be based on a sample of 80 male-male twin pairs. Depression will be assessed by the SCID, HAMD, and the Beck Depression Inventory. Seropositivity to antibodies of a variety of infectious pathogens will be assessing by ELISA methods. Subclinical measures of CAD will include coronary flow reserve (assessed by PET), carotid intima-media thickness (assessed by ultrasound), and flow-mediated dilation of the brachial artery (assessed by ultrasound). Random effects regression methods will be used to determine if depression is associated with infectious pathogen exposure and whether such an association explains the link between depression and subclinical CAD.